294 CHEMISTRY: BANCROFT AND RICHTER PROC. N. A. S. 6 Briggs, D. R., J. Phys. Chem., 32, 641 (1928). 7 Washburn, E. W., J. Am. Chem. Soc., 38, 2431 (1916). 8 Zwaardemakef, H., Chem. Abs., 10, 2837 (1916). 9 Harkins, W. D., and Humphrey, E. C., J. Am. Chem. Soc., 38, 242 (1916.). 10 Kruyt, H. R., Koll. Z., 22, 81 (1918). 11 Kruyt, H. R., and van der Willigen, P. C., Koll. Z., 45, 307 (1928). 12 Freundlich. H., and Rona, P., Sitz. preuss. Akad. Wiss., 20, 397 (1920). REVERSIBLE COAGULA TION IN LIVING TISSUE. II' By WILDER D. BANCROFT AND G. H. RICHTER2 BAKER CHEMICAL LABORATORY, CORNELL UNIVERSITY Read before the Academy April 28, 1931 One function of sodium thiocyanate in living organisms is to increase the dispersion of proteins. That is why it alleviates all troubles due to reversible coagulation of proteins. Borg3 gave 2-10 grains of potassium thiocyanate [it should have been sodium thiocyanate three times a day for one to four weeks to a group of patients suffering from high blood pressure. Quite apart from the change in blood pressure, thirteen de- veloped unspecified unpleasant complications which disappeared within a few days after the drug was discontinued. Toxic psychoses developed in four patients, with disorientation, hallucinations of sight and hearing, mania, confusion, and ideas of persecution, singly or in combination. They lasted only from five to seven days after the drug was stopped. These occurrences were all with patients to whom it had been necessary to give large doses. This means that one form of insanity can be brought on by administra- tion of too much of a dispersing agent. We will call this dispersion in- sanity or Insanity D. This cannot be the only form of insanity, because hysteria often goes over into insanity and this must be due to a coagulation of the brain colloids. We will call this type coagulation insanity or In- sanity C. Shipwrecked sailors in boats often get hallucinations and go insane before jumping overboard or before drinking salt water. This is also a coagulation insanity. There are therefore at least two types of insanity, in one of which the brain colloids remain more or less permanently in the stage of irritability resulting from coagulation, and in the other of which the brain colloids are more or less permanently in a state of over-peptization. These two types can be covered by the statement that insanity is characterized by a more or less permanent, abnormal, degree of dispersion of the brain Downloaded by guest on September 26, 2021 VOL. 17, 1931 CHEMISTR Y: BA NCROFT A ND RICHTER 295 colloids. We are not yet in a position to say what degree of coagulation or over-peptization is characteristic of insanity, except that it must stop short of sleep for Insanity C and must stop short of collapse for Insanity D. It is not claimed that this definition covers all cases of insanity; but it offers a basis of classification which seems likely to be helpful and which seems to cover what might be called the normal types of insanity, where there are no lesions due to obviously abnormal causes. Most of us have been conscious of being temporarily insane at times when waking up in the night, especially if waked suddenly. There are no data to show whether all people always pass through a brief stage of insanity on going to sleep and on waking up, or whether the insanity stage is not usually in the regular sequence but gets shunted in on special occasions. What one decides will depend largely on what one feels about dreams. They are certainly abnormal thinking and the dreams arising from opium or hashish do not differ in anything except persistence from the hallucinations of insanity. The physiologist does not like to call dreams temporary insanity. They certainly do not constitute legal in- sanity and the physiologist does not like the term temporary insanity, though this seems to us a perfectly good concept which should not be left to lawyers in criminal cases. We can represent our present knowledge graphically as follows, dis- persion being at the left and coagulation at the right: Insanity C Sleep or Death, Insanity D, normal, irritability, anesthesia, death Dispersion -< > coagulation It can be left open whether Insanity C always comes in the midst of irritability or only at times. If the former is true, then the region of insanity is ordinarily passed through so rapidly in the case of normal people that they are not conscious of it. In the case of insane people, the insanity stage covers a wide range and the patient does not ordinarily pass out of it to the left at all. It is the reverse of what happens with morphine and caffeine, both alkaloids. Morphine carries the patient rapidly through the irritable stage into sleep and anesthesia. Caffeine takes the patient normally only to the irritable and consequently wakeful stage. If Insanity C is a coagulation phenomenon, addition of a coagulating agent short of sleep or anesthesia should be bad for the patient, while he or she ought to improve when a peptizing agent, such as sodium bromide, is given. Sodium thiocyanate would be better than sodium bromide; but the data are lacking for it or are unknown to us. It is well-known Downloaded by guest on September 26, 2021 296 296zCHEMISTR Y: BANCROFT AND RICHTER PROC. N. A. S. that coffee is bad for most insane patients and this undoubtedly means those suffering from Insanity C. Wright4 has obtained some remarkable results with insane patients by administering 100-300 grains of sodium bromide per day. In regard to one patient he says: "For about four years she was kept in a room and much of the time she was kept in bed. When allowed in the day-room she made impulsive assaults on other patients and employees. She was regarded as dangerous from the fact that she so often attempted to bite people, especially on their ears. In three instances she succeeded, each patient losing part of an ear. Treatment was begun on September 24, 1924. She gradually improved. On No- vember 5 she helped make beds and ran a floor brush. Since that date she has received treatment whenever she has shown a tendency to become irritable. As a result she has become industrious, and helps with the ward work. She has made no assaults for several months past." One of the nurses said: "Before these patients were treated we had to struggle with them every morning to get them bathed and dressed. Then when one was dressed and put in the day room, her anger having been aroused because of the attention necessarily given her, a fight with another patient usually resulted and the combatants had to be separated before further work could be done. This was a frequent occurrence every morning. By the time the patients were finally bathed and dressed, we were all tired out from struggling with them before the day's work had begun." Another nurse stated: "Before the treatment was begun it took four or five of us to bathe and dress these patients. Yesterday morning (i.e., some months after treatment was instituted) I supervised the bathing and dressing of these patients alone." About twenty-five per cent of the patients were classed as unimproved; but Wright does not distinguish two types of insanity and consequently one does not know whether the failures were due to treating the wrong type of patient or to some other cause. In fact, the only way that we can tell that any of Wright's patients suffered from Insanity C is that those are the ones who should be benefited by such a treatment. That is reason- ing in a circle to some extent. Wright does state, however, that "most of the failures have occurred in states of apathy," and we should expect these to be suffering from Insanity D. Wright also says that "in the administration of this drug [sodium bromide] in large doses, constant careful observation on the part of both nurses and physicians of each symptom produced by the drug is very necessary in order to prevent the development of distressing symptoms. Not infrequently patients quickly develop stuporous states or other evidences of a toxic condition which require prompt and energetic treatment. For this reason it is necessary to determine as accurately as possible the tolerance to the drug of each Downloaded by guest on September 26, 2021 VOL. 17, 1931 CHEMISTRY: BA NCROFT AND RICHTER 297 case treated. Unless this is done the administration of the drug is not without danger." This sounds as though Wright were dealing at times with patients suffering from Insanity D or with patients who were carried over by the large amount of bromide from Insanity C to Insanity D. It would have been easy to have distinguished experimentally between these cases. Patients with Insanity C would have been benefited by smaller doses of sodium bromide, while that would not have been the case for patients with Insanity D. The reverse case in which patients with Insanity D are benefited by treatment with a coagulating agent has been studied at Wisconsin though not under this name. Loevenhart, Lorenz, Martin and Malone5 have studied the effect of carbon dioxide, a coagulating agent,6 with very strik- ing results. "The most favorable and striking reaction occurred in those patients who had been mute and mentally inaccessible for long periods of time. In these cases, after a short period of respiratory stimulation, this inaccessibility disappeared and the catatonia passed off.